Effect Of Dark Chocolate On Arterial Function In Healthy Individuals
Introduction
Many epidemiologic studies (study of human disease) have suggested that consuming foods high in flavonoids are linked to decreasing risk of cardiovascular mortality (coronary artery disease and stroke). Many foods are associated with high levels of these beneficial flavonoids such as red wine, green tea, and black tea. Cocoa and chocolate products tend to have the highest amounts of these flavonoids and total antioxidant capacity per weight than most other foods or drinks.
It was investigated whether dark chocolate affects arterial function, and whether the hypothesis that any observed change on the parameters would be associated with antioxidants (flavonoids) contained within the chocolate.
The effect of flavonoid-rich dark chocolate (100g) was analyzed in regards to endothelial function, aortic stiffness, wave reflections, and oxidant status. 17 young healthy volunteers were studied for 3 hours according to a randomized, single-blind, sham procedure-controlled (placebo), cross-over protocol. Data was measured using:
Flow-mediated dilation (FMD) of the brachial artery to evaluate endothelial function.
Aortic augmentation index (AIx) to evaluate wave reflections.
Carotid-femoral pulse wave velocity (PWV) to evaluate aortic stiffness.
Measurement of plasma malondialdehyde (MDA) and total antioxidant capacity (TAC) was used to evaluate plasma oxidant status.
The participants
Healthy young men and women (12 and 5 respectively), aged 24-32. They were not obese, nonsmoking, no diabetes, no hyperlipidemia (ex/ high cholesterol), or any family history of premature vascular disease. None were taking any cardiovascular medications and were clinically well. They abstained from caffeine and alcohol intake for 12 hours beforehand, and from flavonoid-containing foods at least 24 hour beforehand. No females were using oral contraceptives.
Study design
The subjects were studied on 2 separate days. One day involved the chocolate consumption, and one day involved the sham-eating (chewing) placebo. After subjects rested for 20 minutes in the supine position, baseline measurements were taken before each experiment (see Table 1).
They were then randomized to eat 100g of a commercially available, procyanidin-rich dark chocolate (74% cocoa, Noir Intense, Nestle, Vevey, Switzerland) and to drink 250 mL of water. The placebo was to sham-eat (chew) and drink 250 mL of water.
The measurements taken were repeated at 30, 60, 90, 120, 150, and 180 minutes. Venous blood was drawn into tubes containing EDTA (ethylenediaminetetraacetate) at both baseline and at 180 minutes after the chocolate consumption or control.
The chocolate consumed contained 2.62 g per 100g of procyanidins (procyanidin monomers plus dimers 0.54g/100g, trimers through heptamers 0.76g/100g, and the remainder oligomers of greater molecular weight).
Results
Baseline Characteristics
Changes after chocolate or control sessions
The effect of the chocolate is best described as the change in the response of each variable, where the response is defined as net chocolate minus control values at each time point. The P values refer to the repeated measures of ANOVA significance between the chocolate consumption and the control session throughout the study.
Brachial Artery Study
The resting brachial artery diameter increased with chocolate throughout the study period. It increased by 0.15 mm at 90 minutes, and then steadily increased from there (Figure 1, top left graph).
Hyperemic brachial artery diameter also increased with chocolate consumption. (by 0.15 mm at 60 minutes, and reaching 0.18 mm at 180 min.
The flow mediated dilation (FMD) showed a trend to increase with a significant rise at 1 hour after consumption.
The resting brachial artery flow increased with chocolate consumption (by 54.0 mL/min at 90 minutes). There was no significant change in regards to hyperemic brachial artery flow.
Heart Rate, Blood Pressure, Aortic Stiffness, and Wave Reflections
Heart rate increased significantly with chocolate consumption, with a maximum at 180 minutes after consumption by 8.4 beats/min.
The peripheral and central systolic, diastolic, and pulse pressures did not change significantly during this study.
Both augmented pressure and AIx were significantly decreased with chocolate consumption. (Max at 180 min. By 3.2 mm Hg and 10.3% respectively. (Fig. 2). The decrease of AIx remained significant (by 7.8%) even after correction for changes in heart rate.
The pulse wave velocity decreased from 90 minutes onward, reaching a response of -0.28 m/sec at 180 min, but the decrease was not statistically significant.
Plasma Oxidant Status
The plasma TAC or MDA values changed significantly during chocolate consumption indicating no alteration in the oxidant status of the subjects (Fig 3.).
Discussion
This was the first study to demonstrate that dark chocolate has an acute potent dilating effect on muscular arteries (such as the brachial artery) and decreases wave reflections. It does not affect stiffness of large elastic-type arteries such as the aorta. The data indicated that consuming dark chocolate may exert a beneficial effect of endothelial function. These effects are not mediated through an improvement in antioxidant status.
Mechanisms
The predominate mechanism appears to be dilation of small and medium-sized peripheral arteries and arterioles. The results indicate that consuming dark chocolate improves endothelial function. Vasodilator response of arteries decreases as their diameter increases.
Brachial artery response to hyperemia increased despite the fact that the artery dilated under resting conditions.
The results here are in agreement with another study that showed a single dose of cocoa drink reversed endothelial dysfunction in patients with coronary artery disease or at least one with cardiovascular risk factor (Heiss et al, 2003). The results here also align with a study by Fisher et al, which showed flavanol-rich cocoa increased pulsatile blood volume in healthy individuals with a NO-dependent manner (NO being nitric oxide).
An important finding in this study was that contrary to the initial hypothesis, these effects on arterial function are not mediated by a beneficial effect on antioxidants status. There was no increase in plasma antioxidant capacity, and there was a neutral effect of chocolate on lipid peroxidation and oxidative stress within the timeframe of the study. Although there seems to be consensus about the effect of several cocoa products increasing plasma flavonoids, evidence concerning these changes is conflicting (Serafini et al., 2003; Wan et al., 2001). The results here show minimal to no increase in plasma flavonoids.
The dilatory effect of chocolate seems to be attributed to improved NO (nitric oxide) bioavailability, prostacyclin increase, direct effect on chocolate in smooth muscle cells, or activation of central mechanisms. Karim et al has shown cocoa oligomeric procyanidins induce endothelium-dependent relaxation in rabbit aortic rings in vitro, by activating endothelial nitric oxide synthase. In the same study, they found monomeric procyanidins from cocoa did not exhibit the same relaxant response, nor did they active NO synthase even though their antioxidant capacity is well documented. The findings by Karim et al suggest the beneficial effect of cocoa flavonoids on endothelium is not a function of their antioxidant activity, which is consistent with the results found here.
Dark chocolate may increase plasma prostacyclin through modulation of the endothelial cell eicosanoid system pathway by inhibiting cyclooxygenase. This was shown in another study where dark chocolate had the ability to decrease platelet aggregation in healthy individuals (Schramm et al., 2001).
Clinical Implications
The findings here provide a mechanism according to which chocolate and dietary flavonoids in general may exert a protective effect on the cardiovascular system.
Study Limitations
Further research is required to note the implications on other population groups. As well, the question here remains if acute findings can be extrapolated to long-term impact.
Chocolate contains theobromine and caffeine (in small quantities) which could have in theory influenced the results. It has been shown though that caffeine increases aortic stiffness and wave reflections. The observed changes could be due to a net result of the beneficial effect of flavonoids and adverse effect of caffeine.
The control (sham eating) was not a direct control. A chocolate devoid of flavanols would have been more appropriate.
Conclusion
In conclusion, this study shows for the first time that dark chocolate acutely dilates muscular arteries, decreases wave reflections, and may improve endothelial function in healthy humans. These effects do not seem to be mediated through an increase in antioxidant levels. Chocolate consumption may exert a protective effect on the cardiovascular system, and further studies should look at long term effects. The results here suggest studies conducted on arterial function should control for flavonoid intake.